Tablets and method of forming

ABSTRACT

Massecuite Aggregated Total Sugar granules are employed as a binder or binder-filler in the manufacture of compressed tablets, preferably by direct compression of a particulate tableting composition into which the Total Sugar granules have been blended. In some embodiments, the Total Sugar granules also function as an absorbent carrier, and/or as a tablet disintegrator or solubilizer. The Massecuite Aggregated Total Sugar (MATS) granules of high D.E. comprise generally spherical aggregates of cohered microcrystals of dextrose internally containing the residual oligosaccharides of the starch hydrolysis in solid solution, the granules being free-flowing, nonhygroscopic, porous and compressible.

United States Patent Robert E. Brouillard;

Charles L. Griffith, both of Cedar Rapids, Iowa July 15, 1968 Nov. 9,1971 Penick & Ford, Limited Cedar Rapids, Iowa Inventors Appl. No. FiledPatented Assignee TABLETS AND METHOD OF FORMlN 9 Claims, No DrawingsABSTRACT: Massecuite Aggregated Total Sugar granules are employed as abinder or binder-filler in the manufacture of compressed tablets,preferably by direct compression of a particulate tableting compositioninto which the Total Sugar granules have been blended. in someembodiments, the Total Sugar granules also function as an absorbentcarrier, and/or as a tablet disintegrator or solubilizer. The MassecuiteAggregated Total Sugar (MATS) granules of high D.E. comprise generallyspherical aggregates of cohered microcrystals of dextrose internallycontaining the residual oligosaccharides of the starch hydrolysis insolid solution, the granules being freeflowing, nonhygroscopic, porousand compressible.

BACKGROUND The term Total Sugar is applied to starch hydrolyzate sugarmixtures of relatively high D.E. which are produced in solid form, andwhich are usually composed largely of crystalline or anhydrous dextrose,but which also contain residual oligosaccharides of the hydrolysis,which are essentially, noncrystallizable, and are present in the form ofa solid solution. Some of the dextrose may also be present as a glass"or solid solution. in the starch sugar industry, such Total Sugarproducts have been distinguished from crystalline dextrose products,which are produced from high D.E. starch hydrolyzates by crystallizationof the dextrose, and separation of the crystals from the mother liquor,thereby achieving a substantial removal of the oligosaccharides, andresulting in a final crystalline product of DE. 98 percent or higher.This crystalline product is usually obtained as dextrose hydrate, but itcan be dried to produce anhydrous crystalline dextrose.

Heretofore crystalline dextrose, either as the hydrate or anhydrous, hasachieved substantial use as a binder or filler in the production oftablets by wet or dry granulation processes, but not to any appreciableextent in direct compression processes. In direct compression processes,it has been found desirable to employ lactose (milk sugar) or mannitol,notwithstanding the much greater cost of lactose or mannitol thandextrose. Moreover, it appears that heretofore substantially noconsideration at all has been given to the use of Total Sugar as abinder or filler in direct compression processes.

Total Sugar as it is ordinarily produced involves the formation of acrystalline massecuite, which is cast into slabs, dried, and then eithercrushed and ground, or shaved, followed by screening, to produce thefinal powdered or granular product. While this product may contain asmuch as 85-95 percent dextrose, the oligosaccharides in solid solutioncoat the dextrose crystals, and result in a hygroscopic, sticky, andnonfree-flowing product. While such material in small concentrationswould have binder properties in tableting, its nonfreeflowing characteris a serious limitation on use, even in wet or dry-granulationprocesses. Ordinary spray drying of Total Sugar solutions does notproduce significantly better results, the product still beinghygroscopic and sticky, and also tending to be in an unstablecrystalline form.

Although substantial progress has been made in overcoming the problemsassociated with direct compression processes, granulation methods arestill most widely used in tablet preparation, particularly thewet-granulation method. Wet or dry-granulation improves compressibility,but an excessive number of preparatory steps are required, as well asthe undesirable time and labor necessary to carry out the procedure,especially on a large scale. The steps in the wet method are l)weighing, (2) mixing, (3) granulation, (4) screening the damp mass, (5)drying, (6) dry screening, (7) lubrication, and (8) compression.

When tablet ingredients are sensitive to moisture or are unable towithstand elevated temperatures during drying, and when the tabletingredients have sufficient inherent binding or cohesive properties,slugging may be used to form granules. This method'is referred to as drygranulation, precompression, or the double-compression method. While iteliminates some ofthe steps ofthe wet-granulation method, it stillincludes (1) weighing, (2) mixing, (3) slugging, (4) dry screening, (5)lubrication, and (6) compression. Where the active ingredient does nothave sufficient binding or cohesive properties, a binder, orbinder-filler is added prior to slugging. Initially, large tablets aremade as slugs, and then the compressed slugs are ground or otherwisereduced to the desired particle size and sieved.

There is a need for improved binders, such as binder-fillers, in thedry-granulation or slugging process, especially binders having improvedbinding and compressibility properties, while being readily handled andless expensive than many binders presently used. However, an evengreater need has been recognized for improved binders or binder-fillersin direct compression processes. While most of the mechanical problemsof direct compression tableting have now been solved, as indicatedabove, the use of this process is still limited by the need forrelatively expensive binders and fillers, such as spray-dried lactose orspray-dried mannitol.

SUMMARY This invention is based in part on the discovery that a newphysical form of Total Sugar, which is referred to herein as MassecuiteAggregated Total Sugar granules (or as *MATS" granules) has remarkabletableting properties, which make it highly advantageous as a binder orbinder-filler in the formation of compression tablets, especially by themethod of direct compression. MATS granules can also be used as a binderin known granulation processes, and it provides a considerable advantagein the precompression or dry-granulation method of tableting, but itsadvantages are maximized in the direct compression process. In theformation of tablets by direct compression from a particulate mixture,the MATS granules can be blended into the mixture as a partial orcomplete substitute for spray-dried lactose or spray-dried mannitol,resulting in a tableting composition which is free-flowing,compressible, and which produces tablets having excellent cohesiveproperties. The resulting tablets can therefore provide other advantagesof dextrose as a binder or filler, such as taste or organolepticproperties. For example, dextrose hydrate produces a cooling effect whendissolved in the mouth, which can be highly desirable for tableted foodor pharmaceutical products, which are to be chewed or sucked. Thedextrose hydrate can also enhance other flavors in the tablets, whichmay be particularly desirable for tableted food or candy products, suchas candy drops or lozenges containing fruit or spice flavoring agents.

Another advantage of compressed tablets produced with MATS granules isthat while they are highly cohesive and resistant to breakage orcrumbling, they dissolve or disintegrate rapidly in contact with aqueousfluids. This is apparently due not only to the high rate of solubilityof dextrose in microcrystalline form, but also to some extent to thepreservation of the capillary or absorptive capacity of the Total Sugarin the completed tablets. Because of this action, the amount ofdisintegrator additives can be reduced or entirely eliminated.

Still another important advantage of the use of MATS granules in formingcompressed tablets, particularly by direct compression, is that otheradditives can be incorporated in the sugar granules before compressionof the tablets. For example, the Total Sugar granules can be impregnatedwith coloring or flavoring agents, which will effectively color orflavor the completed tablets, and this impregnation will not interferewith the free-flowing character of the granules, and can save time andlabor in preparing the tableting composition. Tableting lubricants,including waxy or oily lubricants, can also be combined with the TotalSugar granules by impregnation. This is particularly desirable where theTotal Sugar granules are used as a filler, that is, in a relatively highconcentration, since in this way sufficient lubrication can be provided,so that it will not be necessary to otherwise add lubricant to thetableting composition. Here again considerable time and labor can besaved. Furthermore, where the tableting composition provides aparticular problem with respect to cohesiveness. auxiliary tabletingbinders can be impregnated into the Total Sugar granules, therebyenhancing the cohesiveness of the total formulation.

It can therefore be seen that for the first time this invention providesa means for utilizing Total Sugar as an effective binder orbinder-filler in compressed tablet formulation. Not only are the MATSgranules superior to ordinary crystalline dextrose in conventionalprocesses, such as dry-granulation processes, but it is adaptable foruse in direct compression processes. This provides a great processimprovement, and the substitution of MATS granules for lactose ormannitol in the formation of tablets by direct compression results in avery large economic saving.

DETAILED DISCUSSION This invention is concerned with the manufacture oftablets by compression as distinguished from molding processes. The termtablets" is used generically and is not intended to be limited to theform of the tablets. While compressed tablets are frequently is discoidform, they may also be round, oval, oblong, cylindrical, triangular,ring-shaped, etc. Compressed tablets are formed from particulatetableting compositions where the ingredients may be in the form ofpowders or granular materials. For introduction into the tabletingmachines, the particulate compositions must be free-flowing. Thetableting composition must also be compressible to a compactive orcohesive state. Still another requirement is that the tabletingcomposition should provide a degree of lubrication.

The basic mechanical unit in all tablet-compression equipment includes alower punch which fits into a die from the bottom and an upper punch,having a head of the same shape and dimensions, which enters the diecavity from the top after the tableting material fills the die cavity.The tablet is formed by pressure applied on the punches and issubsequently ejected from the die. The weight of the tablet isdetermined by the density and the volume of the material which fills thedie cavity. Therefore, the ability of the powder or granulation to fiowfreely into the die is important in insuring a uniform fill, as well asin facilitating the continuous movement of the particulate material fromthe source of supply or feed hopper. If the tablet granulation does notpossess cohesive properties, the tablet after compression will crumbleand fall apart on handling. As the punches must move freely within thedie and the tablet must be readily ejected from the punch faces, thematerial must have a degree of lubrication to minimize friction and toallow for the removal of the compressed tablets.

In general, therefore, this invention is concerned with the manufactu reof compressed tablets and the like wherein increments of a particulatetableting composition are compressed to compacted cohesive tablets. In apreferred embodiment, the tablets are manufactured by direct compressionfrom a free-flowing particulate tableting composition wherein thetableting composition is pressure punched in dies to com pacted cohesivetablets without preparatory granulation thereof. Where necessary, thetableting composition can be subjected to precompaction, includingslugging procedures, or precompaction by forced-flow die feeders, suchas are employed in high speed rotary tableting machines. In suchmachines, compression takes place as the upper and lower punches passbetween a pair of rollers, which produce a slow squeezing effect on thematerial in the die cavity from the top and the bottom, giving a chancefor the entrapped air to escape. The lower punch then lifts up andejects the tablet.

The granular binder or binder-filler for use in the method of thisinvention can be produced by the process described in copendingapplication Ser. No. 674,168, filed Oct. 10, I971, entitled NovelGranular Sugar Products and Process for Producing" now U.S. Pat. No.3,540,927. For the purpose of the present invention, we are concernedwith granular dextrose products produced from starch hydrolyzates ofhigh D.E., which are referred to as Total Sugar" products. Such TotalSugar products are composed of dextrose in admixture with residualoligosaccharides of the saccharification. The process of the citedapplication has sometimes been referred to as Spray Crystallization."However, the product produced by the process can perhaps more accuratelybe described as Spray-Drier Aggregated," as crystallization takes placeprimarily before and after the spray drying step. In addition to theremoval of water, a principal function of the spray drying is to formthe basic aggregate structure with the granular aggregates thus obtainedbeing subsequently aged and dried to complete the process.

More specifically, in the process of the cited application, a watersolution of a crystallizable sugar is subjected to partialcrystallization to form a pumpable massecuite composed essentially ofmicrocrystals of sugar dispersed in a water solution of sugar. Thismassecuite, which may contain from 40 to 60 percent of the sugar incrystalline form, is sprayed into a drying air stream to form atomizeddroplets and to remove part of the water from the droplets in the airstream to form granular aggregates of the microcrystals containingresidual crystallizable sugar solution. Essentially each droplet forms asingle aggregate of generally spherical shape. This step is preferablycarried out in a spray dried tower where the massecuite droplets areformed at the top and fall downwardly through the tower with theevaporation of water therefrom. Where the hydrate crystal form isdesired, the spray dried is operated at a sufficiently low temperatureto avoid formation of anhydrous dextrose or other unstable crystalforms. For example, the massecuite droplets during spray drying of astarch hydrolyzate can be kept below 50 C. With sucrose and othersugars, the spray drying temperature can be varied over a wider range,especially where the sugar has only one crystalline form, such as withsucrose which only forms anhydrous crystals.

The granular crystalline material produced by the spray aggregationprocess just described, will contain additional crystallizable sugar inthe form of a supersaturated solution that will rapidly crystallize.However, the granules obtained from the spray dried have sufficientstructural integrity to permit them to be transferred to otherprocessing apparatus for completion of the crystallization. This furtherprocessing can include an aging procedure in which crystallization iscontinued without removal of much additional water. As a final step,however, it is desirable to subject the granular aggregates to drying toforce completion of the crystallization, and at the same time to reducethe free water content to a very low level. Where part of the watercombines with the sugar as water of crystallization, free water iseliminated in this way as well as by evaporation. The free water contentof the final granular products will usually be below 1 percent byweight, and may be as low as 0.5 percent or lower. Where the granularproduct is formed principally of dextrose monohydrate the total watercontent will be about 9 percent by weight even though there is little orno free water. Overdrying can therefore convert some of the monohydratecrystals to anhydrous crystals. A range of granular products cantherefore be obtained which are useful in the tableting method of thisinvention. For example, the crystalline material of the granules mayconsist substantially entirely of dextrose hydrate, or substantiallyentirely of anhydrous dextrose, or a mixture of the hydrate andanhydrous forms in any desired proportion.

Where the granular tableting material has been prepared by the processof the cited copending application Ser. No. 674,168 from a Total Sugarmassecuite, the material will comprise generally spherical granules ofcrystalline dextrose and the granules will be formed essentially ofaggregates of dextrose microcrystals. The granular size can range fromabout I00 to 400 microns, typically averaging 200-300 microns. The sizedistribution can be modified by screening of the granular product toremove oversize and undersize material. The terms Spray-Drier Aggregatedor SDA refer to Total Sugar granules originating from individualspray-dried droplets of a Total Sugar massecuite comprisingmicrocrystals of dextrose dispersed in a water solution thereof,additional microcrystals of the dextrose having been depositedinternally after the spraying of the droplets. The SDA Total Sugargranules comprise cohered dextrose microcrystals with internal capillarynetworks. Total Sugar granules of the same basic structure (hereingenerically referred to as MATS granules), which are usable for thepurpose of the present invention can also be produced by the process ofcopending application Ser. No. 744,958, filed on even date herewith, andentitled Sugar Granulation Process and Products Produced Thereby." Inthat process a pumpable massecuite consisting of dextrose microcrystalssuspended in a saturated solution of dextrose is intermixed with a bedof previously processed recirculated dextrose which is in the form ofaggregated microcrystals. The mixture is then dried under conditionswhich contribute to the further crystallization of the dextrose insolution as well as to water removal. The final product has the form ofaggregates of cohered dextrose microcrystals and if desired the particlesize can be varied by crushing or grinding and sieving. The fracturedgranules may not be spherical and will have a somewhat more irregularshape than SDA granules, but they are still free-flowing granules andcan be used in the process of the present invention. Consequently, theterms Microcrystalline Aggregated Total Sugar and MATS granules as usedherein are intended to encompass such materials, which are equivalent inproperties to the SDA granules obtained by the process of the citedapplication Ser. No. 674,168.

The D.E. (dextrose equivalent) of the Total Sugar forming the granulesshould be at least 88 percent. MATS granules having a DB. ranging from92 to 98 percent are particularly desirable for compression tableting.Total Sugar granules can be produced having a DB higher than 98 percentby a more complete conversion of the starch hydrolyzate to dextrose.Therefore, if it is desired to employ a filler or binder which issubstantially pure dextrose, Total Sugar granules having a D.E. of from98 to 100 percent can be utilized. In most applications, however, theresidual oligosaccharides in solid solution improve tabletingproperties. The oligosaccharides can function as an auxiliary binder tothe microcrystalline dextrose without interfering with the free-flowingcharacter of the granules, since the oligosaccharide material is withinthe interior of the granules as produced, while becoming available toact as a binder when the granules are crushed during compressiontableting.

In many applications, the MATS granules can advantageously have a totalmoisture content ranging from 8-10 percent, substantially all of thedextrose being in the form of dextrose monohydrate with the free waterless than 1 percent, or preferably less than 0.5 percent. The content ofanhydrous dextrose can be kept below 10 percent. In certain specialapplications, the granules can contain a mixture of anhydrouscrystalline dextrose with crystalline dextrose hydrate, such as from -80percent by weight anhydrous dextrose in admixture with from 80-20percent by weight dextrose hydrate. For example, anhydrous dextrose hasthe ability to absorb free water, which is converted to water ofcrystallization. Thus, anhydrous crystalline dextrose can function as adesiccant for a tableting composition. In such applications, the MATSgranules can contain 90 percent or more of the crystalline dextrose inthe anhydrous form.

While the method of this invention is not limited to any particular enduse of the tablets, the use of MATS granules as a binder or filler willbe most advantageous it is believed in the preparation of tablets forpharmaceutical or food purposes. In pharmaceutical applications, thedextrose can also perform the functions ofa sweetening agent, improvingpalatability for chewable drug tablets, or tablets that are designed asmouth or throat lozenges, and masking the taste of otherwise unpalatableactive ingredients. In food tablet applications, the Total Sugar willitself provide a food component, and in such applications the TotalSugar may be the major ingredient of the tablets, such as with candylozenges, or where the lozenge is partly candy and partly medicinal, aswith cough drops. In general, the tableting process of this inventioncan be used to produce bodies shaped by compression for a wide varietyof articles of commerce, such as candy pieces, lozenges, antiacidmedicaments, drug-containing tablets, convenience foods,color-containing compositions, etc. As previously explained, such bodiescan be shaped by compression on standard tableting machines withoutprior granulation. The tablets will show excellent conformity to moldcharacteristics, and will be cohesive while having easily controllabledisintegration properties. The quantity of MATS granules used in thecompression formulation should at least be sufficient to provide aneffective binder action, and in most applications will be sufficient toserve both as a binder and a filler. Beyond this, such as in the case ofcandy pieces or lozenges, the principal constituent can be the MATSgranules with relatively small amounts of flavorants, colorants, ordrugs. On the other hand, in the case of tablets where MicrocrystallineAggregated Total Sugar is used strictly as a binder, such as with salttablets, as little as 5 percent by weight of the Total Sugar can be usedwhile obtaining excellent processing and tablet characteristics.Speaking broadly, the tablets can contain from 2-98 percent by weight ofthe MATS granules. Effective binding action can frequently be obtainedwith as little as 2-3 percent of the sugar granules, but in mostapplications from 5-10 percent by weight or more is desirable to achieveadequate cohesiveness in the final tablets. Where the sugar granules arealso used as a filler, the amount employed will typically range from atleast 10 percent up to 30 percent by weight or higher. A typical rangefor combined binder and filler properties will be from 5-25 percent byweight.

As previously indicated, additives desired in the completed tablets canin many cases be incorporated in the MATS granules prior to the blendingof the sugar granules with the rest of the tableting formulation. Suchadditives include auxiliary binders, tableting lubricants, flavoringagents, coloring agents, tablet disintegrating agents, etc.

In tableting, the term binders is applied to agents used to impartcohesive qualities to powdered or granular materials. They impart acohesiveness to the tablet formulation which insures the tabletremaining intact after compression.

According to the present invention, the MATS granules are employed as aprincipal binder component of the tablets. However, other tabletingbinders can be used in conjunction with the MATS granules. Binders whichare normally tacky or sticky, and therefore present formulation problemsin maintaining the free-flowing character of the tableting composition,can advantageously be impregnated into and/or coated onto the MATSgranules. For example, water soluble, tacky binders, such as molasses ormalt syrup, gelatin, or natural or synthetic gums, such as acacia,sodium alginate, extract of Irish moss, carboxymethyl cellulose, methylcellulose, polyvinyl-pyrrolidone, etc., can be impregnated into the SDAgranules by the method described in copending application Ser. No.744,642, filed on even date herewith, and entitled Method of CombiningCrystalline Sugar with Modifying Agents and Products Produced Thereby."The binder is dissolved or dispersed in water, and the water dispersionis sprayed on a bed of the MATS granules, while agitating andintermixing the bed. The spray application is at a rate facilitatingrapid coating and absorption of the dispersion from the outer surface ofthe granules into the interiors thereof, and the agitation andintermixing prevents agglomeration of the granules during spraying.Thereafter, the granules can be subjected to drying to remove watertherefrom while leaving the partially or completely dehydrated binder onand within the granules. The percent of binder with which the granulesare impregnated can be increased by the use of a plurality of sprayingand drying cycles. Where the auxiliary binder is organic-solventsoluble, but not water soluble, the granules can be impregnated and/orcoated as also described in the above copending application, filed oneven day herewith.

The methods of the cited copending applications can also be employed forimpregnating the granules with other additives, such as lubricants,flavoring agents, coloring agents, etc. However, the impregnation of thegranules with a lubricant will usually not be a complete substitute forthe incorporation of lubricants in the tableting composition, since thelubricants are designed to provide a number of functions. For example,so-called glidants, which act as flow regulators by improving the flowproperties of the tableting mixture from the feed hopper to the dies,can be directly mixed and blended into the composition rather than beingimpregnated into the granules. Most such glidants are fine powders suchas talc. starch. lycopodium, magnesium stearate, calcium stearate, etc.

Lubricants which perform the function of antiadhesives or antistickingagents are most adaptable to incorporation in the granules, since thegranules will be deformed and ruptured during the compressing of thetablets, thereby releasing the lubricant to perform its function. Thepurpose of antisticking agents is to prevent adhesion of the tabletsurface to the dies and punches during compression. Examples ofantisticking agents are paraffin, stearic acid, cocoa butter, and soaps.Liquid oils, including animal, vegetable, mineral or synthetic oils, canalso be used. Most of these antisticking lubricants are normally liquidor can be liquefied by heating. They can thereby be applied to thegranules as liquids or melts, which are sufficiently liquid to achievepenetration and impregnation of the granules, as well as partial orcomplete surface coating of the granules. In these instances, the MATSgranules function as carriers for the antisticking agent. Whererequired, the antisticking agent can be thinned with an organic solvent,the solvent mixture impregnated into the granules, and the granulesdried to remove the solvent while leaving the antisticking agent, asdescribed in the cited copending applicationentitled Method of CombiningCrystalline Sugar with Modifying Agents and Products Produced Thereby.

Colors in compressed tablets may make the tablets more aesthetic inappearance, but they also help the manufacturer control the productduring its preparation, as well as serving as a means of identificationto the user. Any of the approved water-soluble dyes or mixtures of thesame, may be used to color the tablets by impregnating the MATS granuleswith the colorv This can be conveniently done by dissolving the dye inwater, impregnating the granules, and then drying the granules to removethe water. The impregnation process can be carried out as described inthe cited copending application entitled Method of Combining CrystallineSugar with Modifying Agents and Products Produced Thereby. Thisprocedure is particularly desirable where the granules also function asa filler, such as where the tablets contain from 10-30 percent byweight, or higher percentages.

Where the tablets are designed as lozenges or chewable tablets, such aswhere the tablets are cough drops or candy, flavoring agents can beincorporated in the MATS granules. Flavoring oils in the form of alcoholtinctures can be used to impregnate the granules, by the proceduredescribed in the cited copending application entitled Method ofCombining Crystalline Sugar with Modifying Agents and Products ProducedThereby. Where the flavoring agent is water soluble, as with manysynthetic fruit flavors, a water solution of the flavor can be employedto impregnate the granules, as described in the other above-citedcopending application.

This invention is further illustrated by the following examples in whichthe tablets were all made by direct compression without slugging orregranulation.

EXAMPLE 1 Spray-Dried Aggregated, microcrystalline Total Corn Sugar(92-93 percent dextrose) prepared by the process of U.S. Pat.application No. 674,168, was blended with 0.1 percent by weight ofmagnesium stearate powder. The latter was added as a lubricant toprevent adhering to the die wall or sticking to punch face. The mixturewas placed in a Colton Type Tablet Press and tablets were formed. Thetablets were smooth, uniform, sharp-edged and there was no evidence ofsticking, splitting or capping.

EXAMPLE 2 Spray-Drier Aggregated, microcrystalline Total Corn Sugar(92-93 percent dextrose) prepared by the process of U.S. Pat.application No. 674,168 was dry blended with an antiacid (tetrahydroxydialuminum magnesium carbonate), coloring material, and flavoradditives. The mixture was run in a Colton Tablet Press. The tabletswhich were formed were compact, sharp-edged, and there was no cracking,splitting or capping. The Total Sugar granules gave very good bindingand good strength characteristics. When an attempt was made to runregular commercial crystal dextrose in the same formulation asubstantial percentage of the tablets cracked and all had poor strengthcharacteristics.

EXAMPLE 3 Sodium chloride was blended with 10 percent by weight of SDATotal Corn Sugar (prepared by the process of U.S. Pat. application No.674,168). When pressed in a Colton Tableting Machine the tablets whichwere formed with this mixture were hard, smooth, sharp-edged, and hadexcellent strength characteristics. Very precise and uniform tabletswere obtained and they had a pleasing surface gloss. The sugareffectively masked the unpleasant saline taste associated with most salttablets.

EXAMPLE 4 Two parts of citric acid were dissolved in 30 parts of a 70Brix concentrated grape juice and the mixture was blended into parts ofSDA corn sugar (prepared by the process of U.S. Pat. application No.674,168). After air drying the freeflowing granular product, it wasblended with 0.5 parts of powdered magnesium stearate and tableted in afour pocket Colton tablet press. No sticking to the dies was observedand the tablets showed no splitting or capping. They were smooth,sharp-edged and had excellent strength characteristics. When added tocold water, they dissolved readily to form a clear solution suitable asa fruit drink.

EXAMPLE 5 A water solution of caramel coloring was blended into a bed ofSDA Total Sugar granules and the impregnated granules were dried byheating in a circulating air stream. The resulting free-flowing productwas then readily tableted to give readily soluble, premeasuredquantities of coloring suitable for use in the preparation of foods orbeverages.

EXAMPLE 6 A mixture of vanillin and pure vanilla extract in an alcoholsolution was thoroughly mixed into a bed of SDA Total Sugar granules sothat the resulting impregnated granules consisted of 10 percent byweight of the added solution. Following evaporation of the alcohol, theresulting free-flowing granules were readily tableted to produce smooth,strong, sharp-edged tablets each having the flavoring value ofone-teaspoonful of standard-strength vanilla extract. They were readilysoluble and suitable for use in food preparation.

EXAMPLE 7 A uniform dry blend of the following was prepared: 0.5 percentPrednisone, 0.5 percent powdered magnesium stearate, and 99.0 percentSDA Total Sugar granules (which contained about 0.5 percent freemoisture). The free-flowing mixture was then readily made into 5 grain(total weight) tablets which were hard, smooth, and sharp-edged. Theyhad the desirable feature of dissolving completely in cold water in lessthan four minutes, whereas, tablets using conventional formulationsfrequently take several times that long to dissolve.

EXAMPLE 8 Twenty-seven parts of as-is molasses (containing about 75percent solids) was diluted with 13 parts of water to give a solutioncontaining about 20 parts molasses solids. This was then intimatelymixed into 400 parts of SDA Total Sugar granules and air dried to give afree-flowing product. The product contained approximately 5 percent (onthe original sugar) of the added molasses solids (which is about thesame as the nondextrose solids present in the original sugar) and suitsit to those tableting operations where increased binder strength isdesired.

EXAMPLE 9 An emulsion was prepared of 10 parts 2-fold orange oil(containing 0.1 percent BHT stabilizer) and 0.1 part emulsifier (Tween-)in 20 parts of water in which had been dissolved 4 parts citric acid.The emulsion was then used to impregnate 400 parts of SDA Total Sugargranules which had been vacuum dried down to a total moisture content of1.5 percent. The water in the added emulsion was almost immediatelyabsorbed in converting the anhydrous dextrose to the hydrated form sothat the mixed product was free-flowing without any further drying. Theoil present acted as a die lubricant so that the material was readilytableted without difficulty. The tablets formed dissolved readily togive a pleasant orange flavored beverage.

When in tablet form the additives which can be impregnated into oradmixed with the MATS granules have a reduced exposure to the air sothat their tendency to volatilize or to be oxidized is minimized. Thiscan, in turn, be lessened still further by a coating or encapsulatingoperation performed on the.tablets. Furthermore, the density, hardnessand rate of solution or disintegration can be modified by the selectionof the tableting pressure. Also, where it is desired to control particlesize, and/or the volume of air entrapped in forming the tablets, theMATS granules can be crushed or milled and used in the method of thisapplication. Other advantages have been indicated in the foregoing orwill readily occur to those skilled in the tableting art.

We claim:

1. The method of manufacturing compressed tablets wherein increments ofa tableting composition are compressed to compacted cohesive tablets,characterized by the step of blending into said particulate tabletingcomposition before compression thereof a binder-effective concentrationof starch hydrolyzate sugar in the form of granular aggregates ofdextrose microcrystals, said granular aggregates being generallyspherical and having been aggregated from a microcrystalline massecuiteof a starch hydrolyzate Total Sugar having a DB. of at least 92 percent,said granular aggregates consisting essentially of cohered dextrosemicrocrystals and oligosaccharides in solid solution, said dextrosecrystals being selected from the group consisting of crystallinedextrose hydrate, crystalline anhydrous dextrose, and mixtures thereof.

2. The method of claim 1 in which the major portion of the dextrose ofsaid granular aggregates is in the form of crystalline dextrose hydrate.

3. The method of claim 1 in which the major portion of the dextrose ofsaid granular aggregates is in the form of anhydrous crystallinedextrose.

4. The method of claim 1 wherein said granular aggregates have a D.E. inthe range of 92 to 98 percent and comprise at least 5 percent by weightof said tableting composition.

5. In the method of manufacturing tablets by direct compression from afree-flowing particulate tableting composition wherein the tabletingcomposition is pressure punched in dies to compacted cohesive tabletswithout preparatory granulation thereof, the method characterized by thesteps of blending into said particulate tableting composition withoutessentially changing the free-flowing character thereof, abinder-effective concentration of starch hydrolyzate Total Sugar in theform of free-flowing granular aggregates of dextrose microcrystals, saidgranular aggregates being generally spherical and having beenSpray-Drier Aggregated from a microcrystalline massecuite of a starchhydrolyzate composed of Dextrose and oligosaccharides and having a DB.of at least 92 percent; and thereafter, while said blend remains in saidfree-flowing particulate condition, subjecting increments of said blendto said pressure punching to form said tablets.

6. Compressed tablets produced by the method of claim 5.

7. The method of claim 5 in which said granular aggregates have a D.E.within the range from 92 to 98 percent, and comprise at least 5 percentby weight of said blend.

8. The method improvement of claim 5 in which said granular aggregatescomprise from 10 to 30 percent by weight of said tableting composition,thereby serving as both a filler and binder.

9. The method improvement of claim 5 in which said granular aggregatesprior to blending with said tableting composition are impregnated with atablet additive carried in a water base impregnating vehicle.

2. The method of claim 1 in which the major portion of the dextrose ofsaid granular aggregates is in the form of crystalline dextrose hydrate.3. The method of claim 1 in which the major portion of the dextrose ofsaid granular aggregates is in the form of anhydrous crystallinedextrose.
 4. The method of claim 1 wherein said granular aggregates havea D.E. in the range of 92 to 98 percent and comprise at least 5 percentby weight of said tableting composition.
 5. In the method ofmanufacturing tablets by direct compression from a free-flowingparticulate tableting composition wherein the tableting composition ispressure punched in dies to compacted cohesive tablets withoutpreparatory granulation thereof, the method characterized by the stepsof blending into said particulate tableting composition withoutessentially changing the free-flowing character thereof, abinder-effective concentration of starch hydrolyzate Total Sugar in theform of free-flowing granular aggregates of dextrose microcrystals, saidgranular aggregates being generally spherical and having beenSpray-Drier Aggregated from a microcrystalline massecuite of a starchhydrolyzate composed of Dextrose and oligosaccharides and having a D.E.of at least 92 percent; and thereafter, while said blend remains in saidfree-flowing particulate condition, subjecting increments of said blendto said pressure punching to form said tablets.
 6. Compressed tabletsproduced by the method of claim
 5. 7. The method of claim 5 in whichsaid granular aggregates have a D.E. within the range from 92 to 98percent, and comprise at least 5 percent by weight of said blend.
 8. Themethod improvement of claim 5 in which said granular aggregates comprisefrom 10 to 30 percent by weight of said tableting composition, therebyserving as both a filler and binder.
 9. The method improvement of claim5 in which said granular aggregates prior to blending with saidtableting composition are impregnated with a tablet additive carried ina water base impregnating vehicle.